A human antibody potently neutralizes RSV by targeting the conserved hydrophobic region of prefusion F

doi:10.1007/s11427-022-2250-0

	A human antibody potently neutralizes RSV by targeting the conserved hydrophobic region of prefusion F
	Yi, Chunyan 1; Su, Caixia 3; Sun, Xiaoyu 1,5; Lu, Xiao 1; Si, Chuanya 1; Liu, Caixuan 1; Yang, Zhuo 1; Yuan, Hong 4; Huang, Yuying 1; Wen, Jing 1; He, Yonghui 1; Zhang, Yaguang 1; Ma, Liyan 1; Cong, Yao 1; Zhao, Gan 3; Ling, Zhiyang 1; Wang, Bin 3; Sun, Bing1,2
	2023
发表期刊	SCIENCE CHINA LIFE SCIENCES; (IF:8.0[JCR-2023],7.3[5-Year])
ISSN	1674-7305
EISSN	1869-1889
DOI	10.1007/s11427-022-2250-0
摘要	Respiratory syncytial virus (RSV) continues to pose serious threats to pediatric populations due to the lack of a vaccine and effective antiviral drugs. RSV fusion (F) glycoprotein mediates viral-host membrane fusion and is a key target for neutralizing antibodies. We generated 23 full-human monoclonal antibodies (hmAbs) against prefusion F protein (pre-F) from a healthy adult with natural RSV infection by single B cell cloning technique. A highly potent RSV-neutralizing hmAb, named as 25−20, is selected, which targets a new site Ø-specific epitope. Site-directed mutagenesis and structural modelling analysis demonstrated that 25−20 mainly targets a highly conserved hydrophobic region located at the a4 helix and a1 helix of pre-F, indicating a site of vulnerability for drug and vaccine design. It is worth noting that 25−20 uses an unreported inferred germline (iGL) that binds very poorly to pre-F, thus high levels of somatic mutations are needed to gain high binding affinity with pre-F. Our observation helps to understand the evolution of RSV antibody during natural infection. Furthermore, by in silico prediction and experimental verification, we optimized 25−20 with KD values as low as picomolar range. Therefore, the optimized 25−20 represents an excellent candidate for passive protection against RSV infection.
关键词	affinity maturation conserved epitope human antibody potent neutralization RSV somatic mutations
学科门类	Biochemistry, Genetics and Molecular Biology (all) ; Environmental Science (all) ; Agricultural and Biological Sciences (all)
URL	查看原文
收录类别	SCOPUS
语种	英语
原始文献类型	Article
Scopus 记录号	2-s2.0-85149028994
来源库	SCOPUS
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/286490
专题	生命科学与技术学院生命科学与技术学院_特聘教授组_孙兵组
作者单位	1.State Key Laboratory of Cell Biology,Shanghai Institute of Biochemistry and Cell Biology,Center for Excellence in Molecular Cell Science,Chinese Academy of Sciences; University of Chinese Academy of Sciences,Shanghai,200031,China; 2.School of Life Science and Technology,ShanghaiTech University,Shanghai,201210,China; 3.Key Laboratory of Medical Molecular Virology (MOE/MOH),Department of Medical Microbiology and Parasitology,School of Basic Medical Sciences,Shanghai Medical College,Fudan University,Shanghai,200032,China; 4.MedimScience.Co,Hangzhou,311217,China; 5.Shanghai Institute of Infectious Disease and Biosecurity,Shanghai Medical College,Fudan University,Shanghai,200032,China
推荐引用方式 GB/T 7714	Yi, Chunyan,Su, Caixia,Sun, Xiaoyu,et al. A human antibody potently neutralizes RSV by targeting the conserved hydrophobic region of prefusion F[J]. SCIENCE CHINA LIFE SCIENCES;,2023.
APA	Yi, Chunyan.,Su, Caixia.,Sun, Xiaoyu.,Lu, Xiao.,Si, Chuanya.,...&Sun, Bing.(2023).A human antibody potently neutralizes RSV by targeting the conserved hydrophobic region of prefusion F.SCIENCE CHINA LIFE SCIENCES;.
MLA	Yi, Chunyan,et al."A human antibody potently neutralizes RSV by targeting the conserved hydrophobic region of prefusion F".SCIENCE CHINA LIFE SCIENCES; (2023).